Dengue is an important global health problem that is increasing in geographic range and epidemic severity each year. This research project will address critical gaps in our understanding of the epidemiology and pathogenesis of dengue illnesses. Specific aims. The major aims of this research will be: (1) to evaluate the association of prior flavivirus immunity with DHF, as well as the association of infecting dengue serotype and the outcome of primary and secondary infections; (2) to better define the spectrum of clinical presentations in dengue illness and to develop and test more sensitive and specific case definitions; to use hospital-based data to evaluate predictors of progression to DHF and dengue shock syndrome (DSS) to guide early intervention; (3) to evaluate how and why the demographics and distribution of dengue viruses have changed over time in Thailand. Research Desiqn. The research will involve both existing datasets and primary data collection in Bangkok, Thailand, and AFRIMS' dengue field site in Kamphaeng Phet Province (KPP), Thailand. 30 years of passive surveillance data on DHF hospitalizations have been collected in Bangkok, with 12 years of more detailed clinical data from children hospitalized with dengue at Queen Sirikit National Children's Hospital in Bangkok. A prospective study in KPP has collected data on symptomatic dengue illnesses and asymptomatic seroconversion in cohorts of school-aged children since 1998, with a cluster component for viremic cases added for the period 2003-2008. Methods. The effects of prior flavivirus immunity will be evaluated using the KPP cohort data which include information on the presence/absence of antibodies to Japanese Encephalitis at enrollment, the clinical severity of incident dengue illnesses, and whether the infection represented a primary, secondary, or post-secondary infection. Case definitions will be tested and modified by incorporating existing data into predictive models, with evaluation of sensitivity, specificity and Receiver Operating Characteristic curves. Predictors for progression to DHF will be assessed based upon laboratory markers and clinical characteristics on admission to the hospital. "Best fit" models for case definitions and predictors of progression to DHF will then be tested prospectively. Changes in the demographics and transmission patterns of dengue infections will be assessed, including whether and how the mean age of DHF has increased. Siqnificance. Dengue is an important global health problem. This research will address key questions in the epidemiology, virology, and immunology of dengue viruses and dengue illness. [unreadable] [unreadable] [unreadable] [unreadable]